Trial Outcomes & Findings for A Study Measuring Effect of LY2140023 (Pomaglumetad Methionil) on Electrocardiographs in Participants With Schizophrenia (NCT NCT01606436)
NCT ID: NCT01606436
Last Updated: 2023-04-03
Results Overview
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. QT intervals from quadruplicate electrocardiogram (ECG) data were corrected for heart rate using Fridericia's formula: QTcF = QT/RR\^0.333, where RR is the interval between two R waves. Least squares (LS) mean changes from baseline in QTcF were calculated using a mixed-effects model with baseline QTcF, treatment, time, period, sequence, and the time-by-treatment interaction as fixed effects and participant and the participant-by-period interaction as random effects.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
86 participants
Primary outcome timeframe
Baseline, up to 12 hours postdose in each treatment period
Results posted on
2023-04-03
Participant Flow
All participants had to go through a lead in 7-day antipsychotic medication washout.
Participant milestones
| Measure |
LY2140023 Then Placebo Then Moxifloxacin
Single 400-mg oral dose of LY2140023 - Day 8 Washout - Days 9-10 Single oral dose of LY2140023-matched placebo - Day 11 Washout - Day 12-13 Single 400-mg oral dose of moxifloxacin (Avelox) - Day 14 Washout - Day 15-16
|
Placebo Then Moxifloxacin Then LY2140023
Single oral dose of LY2140023-matched placebo- Day 8 Washout - Days 9-10 Single 400-mg oral dose of moxifloxacin (Avelox)- Day 11 Washout - Day 12-13 Single 400-mg oral dose of LY2140023 - Day 14 Washout - Day 15-16
|
Moxifloxacin Then LY2140023 Then Placebo
Single 400-mg oral dose of moxifloxacin (Avelox)- Day 8 Washout - Day 9-10 Single 400-mg oral dose of LY2140023 - Day 11 Washout - Day 12-13 Single oral dose of LY2140023-matched placebo- Day 14 Washout - Days 15-16
|
Placebo Then LY2140023 Then Moxifloxacin
Single 400-mg oral dose of placebo- Day 8 Washout - Day 9-10 Single 400-mg oral dose of LY2140023- Day 11 Washout - Day 12-13 Single oral dose of moxifloxacin (Avelox) - Day 14 Washout - Days 15-16
|
Moxifloxacin the Placebo Then LY2140023
Single oral dose of moxifloxacin (Avelox) - Day 8 Washout - Day 9-10 Single 400-mg oral dose of placebo- Day 11 Washout - Day 12-13 Single 400-mg oral dose of LY2140023- Day 14 Washout - Days 15-16
|
LY2140023the Moxifloxacin the Placebo
Single 400-mg oral dose of LY2140023- Day 8 Washout - Day 9-10 Single oral dose of moxifloxacin (Avelox) - Day 11 Washout - Day 12-13 Single 400-mg oral dose of placebo- Day 14 Washout - Days 15-16
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
14
|
14
|
14
|
14
|
13
|
14
|
|
Overall Study
Received First Intervention
|
14
|
14
|
14
|
14
|
13
|
14
|
|
Overall Study
Received Second Intervention
|
14
|
14
|
14
|
14
|
12
|
14
|
|
Overall Study
Received Third Intervention
|
14
|
14
|
12
|
12
|
12
|
14
|
|
Overall Study
COMPLETED
|
14
|
14
|
12
|
12
|
12
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
2
|
2
|
1
|
0
|
Reasons for withdrawal
| Measure |
LY2140023 Then Placebo Then Moxifloxacin
Single 400-mg oral dose of LY2140023 - Day 8 Washout - Days 9-10 Single oral dose of LY2140023-matched placebo - Day 11 Washout - Day 12-13 Single 400-mg oral dose of moxifloxacin (Avelox) - Day 14 Washout - Day 15-16
|
Placebo Then Moxifloxacin Then LY2140023
Single oral dose of LY2140023-matched placebo- Day 8 Washout - Days 9-10 Single 400-mg oral dose of moxifloxacin (Avelox)- Day 11 Washout - Day 12-13 Single 400-mg oral dose of LY2140023 - Day 14 Washout - Day 15-16
|
Moxifloxacin Then LY2140023 Then Placebo
Single 400-mg oral dose of moxifloxacin (Avelox)- Day 8 Washout - Day 9-10 Single 400-mg oral dose of LY2140023 - Day 11 Washout - Day 12-13 Single oral dose of LY2140023-matched placebo- Day 14 Washout - Days 15-16
|
Placebo Then LY2140023 Then Moxifloxacin
Single 400-mg oral dose of placebo- Day 8 Washout - Day 9-10 Single 400-mg oral dose of LY2140023- Day 11 Washout - Day 12-13 Single oral dose of moxifloxacin (Avelox) - Day 14 Washout - Days 15-16
|
Moxifloxacin the Placebo Then LY2140023
Single oral dose of moxifloxacin (Avelox) - Day 8 Washout - Day 9-10 Single 400-mg oral dose of placebo- Day 11 Washout - Day 12-13 Single 400-mg oral dose of LY2140023- Day 14 Washout - Days 15-16
|
LY2140023the Moxifloxacin the Placebo
Single 400-mg oral dose of LY2140023- Day 8 Washout - Day 9-10 Single oral dose of moxifloxacin (Avelox) - Day 11 Washout - Day 12-13 Single 400-mg oral dose of placebo- Day 14 Washout - Days 15-16
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
1
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Sponsor Decision
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Study Measuring Effect of LY2140023 (Pomaglumetad Methionil) on Electrocardiographs in Participants With Schizophrenia
Baseline characteristics by cohort
| Measure |
Overall
n=86 Participants
After completing a 7-day antipsychotic medication washout period (Days 1 to 7), participants still meeting eligibility criteria were randomized to receive single doses of LY2140023 (Treatment A), matching placebo (Treatment B), and moxifloxacin (Treatment C) in 1 of 6 treatment sequences (ABC, BCA, CAB, BAC, CBA, or ACB). Study drug was administered on Days 8, 11, and 14 of the study.
LY2140023 (pomaglumetad methionil): 400 milligrams (mg) (5 x 80 mg tablets), administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
placebo: 5 tablets, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
moxifloxacin: 400 mg tablet, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
|---|---|
|
Age, Continuous
|
40.3 years
STANDARD_DEVIATION 10.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
84 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
65 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
17 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
86 participants
n=5 Participants
|
|
Weight
|
86.73 kilograms
STANDARD_DEVIATION 15.76 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, up to 12 hours postdose in each treatment periodPopulation: All participants who received at least 1 dose of LY2140023, moxifloxacin, or placebo and had evaluable QTcF data
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. QT intervals from quadruplicate electrocardiogram (ECG) data were corrected for heart rate using Fridericia's formula: QTcF = QT/RR\^0.333, where RR is the interval between two R waves. Least squares (LS) mean changes from baseline in QTcF were calculated using a mixed-effects model with baseline QTcF, treatment, time, period, sequence, and the time-by-treatment interaction as fixed effects and participant and the participant-by-period interaction as random effects.
Outcome measures
| Measure |
400 mg LY2140023
n=81 Participants
LY2140023 (pomaglumetad methionil): 400 milligrams (mg) (5 x 80 mg tablets), administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
400 mg Moxifloxacin
n=82 Participants
moxifloxacin: 400 mg tablet, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
Placebo
n=80 Participants
placebo: 5 tablets, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
|---|---|---|---|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
0.5 hours
|
-7.1 milliseconds
Interval -8.5 to -5.6
|
-6.66 milliseconds
Interval -8.21 to -5.11
|
-7.7 milliseconds
Interval -9.2 to -6.2
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
2.0 hours
|
-4.7 milliseconds
Interval -6.2 to -3.2
|
-2.62 milliseconds
Interval -4.18 to -1.07
|
-7.6 milliseconds
Interval -9.1 to -6.1
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
3.0 hours
|
-4.0 milliseconds
Interval -5.5 to -2.5
|
0.23 milliseconds
Interval -1.32 to 1.77
|
-6.1 milliseconds
Interval -7.5 to -4.6
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
4.0 hours
|
-1.4 milliseconds
Interval -2.9 to 0.2
|
3.52 milliseconds
Interval 1.98 to 5.07
|
-2.8 milliseconds
Interval -4.3 to -1.4
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
5.0 hours
|
-2.0 milliseconds
Interval -3.5 to -0.5
|
—
|
-3.5 milliseconds
Interval -5.0 to -2.0
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
6.0 hours
|
-2.6 milliseconds
Interval -4.1 to -1.1
|
—
|
-6.1 milliseconds
Interval -7.6 to -4.6
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
8.0 hours
|
-5.8 milliseconds
Interval -7.3 to -4.3
|
—
|
-7.9 milliseconds
Interval -9.4 to -6.4
|
|
Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
12.0 hours
|
-6.3 milliseconds
Interval -7.8 to -4.8
|
-3.25 milliseconds
Interval -4.81 to -1.69
|
-8.0 milliseconds
Interval -9.5 to -6.5
|
Adverse Events
400 mg LY2140023
Serious events: 1 serious events
Other events: 52 other events
Deaths: 0 deaths
400 mg Moxifloxican
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
400 mg LY2140023
n=81 participants at risk
LY2140023 (pomaglumetad methionil): 400 milligrams (mg) (5 x 80 mg tablets), administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
400 mg Moxifloxican
n=82 participants at risk
moxifloxacin: 400 mg tablet, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
Placebo
n=80 participants at risk
placebo: 5 tablets, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
|---|---|---|---|
|
Nervous system disorders
Convulsion
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
Other adverse events
| Measure |
400 mg LY2140023
n=81 participants at risk
LY2140023 (pomaglumetad methionil): 400 milligrams (mg) (5 x 80 mg tablets), administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
400 mg Moxifloxican
n=82 participants at risk
moxifloxacin: 400 mg tablet, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
Placebo
n=80 participants at risk
placebo: 5 tablets, administered orally as a single dose during 1 of 3 treatment periods separated by 2-day washout periods.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.5%
2/81 • Number of events 2
|
0.00%
0/82
|
0.00%
0/80
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Eye disorders
Eye irritation
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Eye disorders
Visual impairment
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/81
|
2.4%
2/82 • Number of events 2
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/81
|
0.00%
0/82
|
2.5%
2/80 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
3.7%
3/81 • Number of events 3
|
1.2%
1/82 • Number of events 1
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Gingivitis
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Gastrointestinal disorders
Lip oedema
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Gastrointestinal disorders
Nausea
|
22.2%
18/81 • Number of events 18
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Retching
|
1.2%
1/81 • Number of events 2
|
0.00%
0/82
|
0.00%
0/80
|
|
Gastrointestinal disorders
Tongue disorder
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
22.2%
18/81 • Number of events 21
|
0.00%
0/82
|
0.00%
0/80
|
|
General disorders
Pain
|
0.00%
0/81
|
1.2%
1/82 • Number of events 1
|
0.00%
0/80
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Infections and infestations
Rash pustular
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/81
|
1.2%
1/82 • Number of events 1
|
0.00%
0/80
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/81
|
1.2%
1/82 • Number of events 1
|
0.00%
0/80
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.5%
2/81 • Number of events 2
|
0.00%
0/82
|
0.00%
0/80
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
1.2%
1/81 • Number of events 1
|
1.2%
1/82 • Number of events 1
|
0.00%
0/80
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/81
|
1.2%
1/82 • Number of events 1
|
0.00%
0/80
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Nervous system disorders
Dizziness
|
18.5%
15/81 • Number of events 17
|
3.7%
3/82 • Number of events 3
|
2.5%
2/80 • Number of events 2
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Nervous system disorders
Dystonia
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Nervous system disorders
Extrapyramidal disorder
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Nervous system disorders
Headache
|
8.6%
7/81 • Number of events 9
|
4.9%
4/82 • Number of events 4
|
2.5%
2/80 • Number of events 2
|
|
Nervous system disorders
Nystagmus
|
2.5%
2/81 • Number of events 2
|
0.00%
0/82
|
0.00%
0/80
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Nervous system disorders
Sedation
|
2.5%
2/81 • Number of events 2
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Nervous system disorders
Tremor
|
2.5%
2/81 • Number of events 2
|
0.00%
0/82
|
0.00%
0/80
|
|
Psychiatric disorders
Anxiety
|
4.9%
4/81 • Number of events 4
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/81
|
0.00%
0/82
|
3.8%
3/80 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/81
|
1.2%
1/82 • Number of events 1
|
1.2%
1/80 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/81
|
0.00%
0/82
|
1.2%
1/80 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.2%
1/81 • Number of events 1
|
0.00%
0/82
|
0.00%
0/80
|
|
Vascular disorders
Hot flush
|
0.00%
0/81
|
1.2%
1/82 • Number of events 1
|
0.00%
0/80
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60